Synthesis and characterisation of phenanthroline-oxazine ligands and their Ag(I), Mn(II) and Cu(II) complexes and their evaluation as antibacterial agents

Abstract

A series of phenanthroline-oxazine ligands were formed by a cyclisation reaction between L-tyrosine amino acid esters and 1,10-phenanthroline-5,6-dione (phendione). The methyl derivative of the phenanthroline-oxazine ligand 1 was complexed with Ag(I), Mn(II) and Cu(II) to form [Ag(1) 2 ]ClO 4 , [Mn(1) 3 ](ClO 4 ) 2 and [Cu(1) 3 ](ClO 4 ) 2 . The activity of these metal complexes was tested against the bacteria Escherichia coli and Staphylococcus aureus. Each of the metal complexes was more active than 1 against S. aureus and the Mn(II) and Cu(II) complexes also showed greater activity than 1 towards E. coli. The effect of increasing the length of the alkyl moiety on the phenanthroline-oxazine ligands and their corresponding tris homoleptic Cu(II) complexes was investigated. In all cases both the ligands and their complexes were more active against Gram-positive S. aureus than against Gram-negative E. coli. Differences in the lipophilicity of the ligands and their corresponding Cu(II) complexes did alter the antibacterial activity, with the hexyl and octyl derivatives and their complexes showing the greatest activity and comparing well with clinically used antibiotics. The most active Cu(II) complexes and their respective ligands were also active against Methicillin-resistant S. aureus (MRSA). In vivo toxicity studies, conducted using the Galleria mellonella model, showed that all of the compounds were well tolerated by the insect larvae.

Multi-target activity of copper complexes: Antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor

“…It is well known that chelation is not the only criterion for antibacterial activity. Some important factors such as the nature of the metal ion, the nature of the ligand, the coordinating sites, the geometry of the complex, the concentration, hydrophilicity, lipophilicity, and the presence of co-ligands have a considerable influence on the antibacterial activity [ [34] , [35] , [36] ]. Complexes containing heterocyclic ligands have a more possibility of interacting with nucleoside ases [ 37 ].…”

A polynuclear CuIIBiIII complex with antipyrine‐derived Schiff‐base: Preparation, characterization, and biological evaluations

“…In previously reported literatures, the Bi-O bond distances are usually in the range from 2.064(7) to 3.455(2) Å. [37][38][39][40][41] Cu-O bond distances are in the range of 1.858 (19)…”

“…As pathogenic microorganisms may spread directly from one person to another or indirectly through surface contamination, developing new copper antibacterial drugs and their mechanism of action have been the focus of researchers. The mechanism of microbial death caused by copper is debatable, and the significance and contribution of each mechanism are unknown 19 …”

“…The mechanism of microbial death caused by copper is debatable, and the significance and contribution of each mechanism are unknown. 19 Schiff bases are constructed by azomethine (-HC=N-) characteristic groups and formed via the condensation reaction between aldehydes or ketones and primary amines. 20 In recent years, they have been favored by many researchers owing to their flexible synthesis, diverse coordination modes, excellent biological properties, and high medicinal utility.…”

Synthesis, characterisation, and solution behaviour of Ag(I) bis(phenanthroline-oxazine) complexes and the evaluation of their biological activity against the pathogenic yeast Candida albicans

“…The Ag(I) and Cu(II) bis -complexes of 1 showed stronger binding to calf-thymus DNA than their phen analogues or the minor groove binding drugs, pentamidine and netropsin (McCann et al 2013 ). We previously carried out a study focused on the antibacterial ( Escherichia coli, Staphylococcus aureus and methicillin-resistant S. aureus (MRSA)) properties of Cu(II) complexes of 1 and a series of more lipophilic analogues (Ahmed et al 2022 ). These studies showed that the lipophilicity of the ligand did influence the antibacterial activity, with the complexes containing the hexyl and octyl alkyl chains showing the highest activity.…”